1. Field of the Invention
The invention relates to a mucin peptide with immunoenhancing properties, pharmaceutical compositions containing the peptide, and methods of treating or preventing cancer.
2. Background Information
The MUC1 gene is expressed in normal epithelium and several types of human cancers and at very high levels in breast tumors (1). A major product of this gene is a polymorphic type 1 transmembrane molecule consisting of a large, heavily glycosylated extracellular domain, a transmembrane domain, and a 72 amino acid cytoplasmic tail (2). The polymorphism mainly derives from variations in the numbers of a 20 amino acid tandem repeat unit present in the extracellular domain. A secreted MUC1 isoform (MUC1/sec) (3) has also been found, that includes a sequence of intron 2, terminates prematurely at a stop codon within this intron, and is therefore devoid of the transmembrane domain.
MUC1 and fragments and derivatives thereof have been widely studied for possible use in anticancer vaccines and cancer therapy. U.S. Pat. No. 6,344,203 discloses peptides that mimic MUC1 and bind to IB4 lectin and anti-Gal.alpha.(1,3)Gal antibodies, for use in a cancer vaccine. The peptides are conjugated to carrier proteins such as tetanus toxoid, diphtheria toxoid or oxidized KLH in order to stimulate T cell help.
U.S. Pat. No. 5,827,666 discloses a synthetic MUC1 peptide comprising at least two 20-amino acid tandem repeats of MUC1 that is capable of attaining native conformation in the absence of glycosylation. The synthetic peptide is indicated to be useful, inter alia, in a vaccine that also includes an amino acid sequence for an epitope. U.S. Pat. No. 5,989,552 discloses a conjugate of a MUC1 polypeptide or tandem repeats thereof and oxidized mannan, for use in immunotherapy.
U.S. Pat. No. 6,080,725 discloses saponin analog adjuvants that may be utilized with MUC1 and peptide fragments thereof as tumor-associated antigens in a vaccine.
MUC1 has also been described and used as a cancer cell determinant or marker, as disclosed, for example, in published U.S. patent application Ser. Nos. 20020009759, 20020012931, 20020022235, and 20010051351.
In the aforementioned disclosures, MUC1, and fragments and mimics thereof are utilized as or considered to be tumor-associated antigens for use in vaccines or immunogenic compositions, or as markers for diagnostic tests.
In the present invention the unexpected discovery was made that a variant secretory isoform of MUC1 has the properties of an adjuvant, and thus has immunoenhancing properties that are distinct from those of an antigen.